Human umbilical cord mesenchymal stem cell-derived exosomes promote murine skin wound healing by neutrophil and macrophage modulations revealed by single-cell RNA sequencing

被引：25

作者：

Liu, Yuanyuan ^{[1
,2
]}

Zhang, Mingwang ^{[3
]}

Liao, Yong ^{[2
]}

Chen, Hongbo ^{[4
]}

Su, Dandan ^{[4
]}

Tao, Yuandong ^{[5
]}

Li, Jiangbo ^{[6
]}

Luo, Kai ^{[7
]}

Wu, Lihua ^{[7
]}

Zhang, Xingyue ^{[2
]}

Yang, Rongya ^{[2
]}

机构：

[1] Chinese Peoples Liberat Army, Med Sch, Beijing, Peoples R China

[2] Chinese Peoples Liberat Army PLA Gen Hosp, Med Ctr 7, Dept Dermatol, Beijing, Peoples R China

[3] Army Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China

[4] Sun Yat Sen Univ, Sch Pharmaceut Sci, Shenzhen, Peoples R China

[5] Chinese Peoples Liberat Army PLA Gen Hosp, Med Ctr 7, Dept Pediat Urol, Beijing, Peoples R China

[6] Acad Mil Med Sci, Bioinformat Ctr, Beijing, Peoples R China

[7] Chinese Peoples Liberat Army PLA Gen Hosp, Biomed Treatment Ctr, Med Ctr 7, Beijing, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷

基金：

中国国家自然科学基金;

关键词：

exosomes; wound healing; single-cell RNA sequencing; cellular heterogeneity; neutrophils; macrophages; INHIBITORY FACTOR; TGF-BETA; INFILTRATION; SUPPRESSION; INFLAMMATION; FIBROBLASTS; EXPRESSION; DEPLETION; IMMUNITY; THERAPY;

D O I：

10.3389/fimmu.2023.1142088

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

IntroductionFull-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing. MethodsUtilizing single-cell RNA sequencing, the transcriptomic diversity of neutrophils and macrophages was analyzed in order to predict the cellular fate of these immune cells under the influence of hucMSC-Exosomes and to identify alterations of ligand-receptor interactions that may influence the wound microenvironment. The validity of the findings obtained from this analysis was subsequently corroborated by immunofluorescence, ELISA, and qRT-PCR. Neutrophil origins were characterized based on RNA velocity profiles. ResultsThe expression of RETNLG and SLC2A3 was associated with migrating neutrophils, while BCL2A1B was linked to proliferating neutrophils. The hucMSC-Exosomes group exhibited significantly higher levels of M1 macrophages (215 vs 76, p < 0.00001), M2 macrophages (1231 vs 670, p < 0.00001), and neutrophils (930 vs 157, p < 0.00001) when compared to control group. Additionally, it was observed that hucMSC-Exosomes elicit alterations in the differentiation trajectories of macrophages towards more anti-inflammatory phenotypes, concomitant with changes in ligand-receptor interactions, thereby facilitating healing. DiscussionThis study has revealed the transcriptomic heterogeneity of neutrophils and macrophages in the context of skin wound repair following hucMSC-Exosomes interventions, providing a deeper understanding of cellular responses to hucMSC-Exosomes, a rising target of wound healing intervention.

引用

页数：16

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